tbuckley/cabot-search huggingface dataset:
A toolbox of different approaches to analyze and present PRO-CTCAE data in oncology studies
Authors: Antoine Regnault, Angély Loubert, Boris Gorsh, Randy Davis, Anna Cardellino, Kristin Creel, Stéphane Quéré, Sandhya Sapra, Linda Nelsen, Laurie Eliason
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background The patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is used to assess symptomatic adverse events in oncology trials. Currently, no standard for PRO-CTCAE analysis exists. Methods Key methods of descriptive analysis and longitudinal modeling using PRO-CTCAE data from an oncology clinical trial, DRiving Excellence in Approaches to Multiple Myeloma-2 (DREAMM-2), a phase II trial of belantamab mafodotin in multiple myeloma (NCT03525678), were explored. Descriptive methods included maximum postbaseline ratings, mean change over time, ratings above a predefined cutoff, line graphs, and stacked bar charts to illustrate patient-reported adverse events at one timepoint or dynamics over time. Analysis methods involving modeling over time included toxicity over time (ToxT) (repeated measurement model, time-to-event, area under the curve analyses), generalized estimating equations (GEE), and ordinal log-linear models (OLLMs). Results Visualizations of PRO-CTCAE data highlighted different aspects of the data. Selection of the appropriate visualization will depend on the audience and message to be conveyed. Consistent results were obtained by all modeling approaches; no difference was found between dose groups of the DREAMM-2 study in any PRO-CTCAE item by the ToxT approach or the more sophisticated GEE and OLLM methods. Interpretation of GEE results was the most challenging. OLLM supported the interval nature of the PRO-CTCAE response scale in the DREAMM-2 study. All modeling approaches account for multiple testing (driven by the number of items). Conclusions Descriptive analyses and longitudinal modeling approaches are complementary approaches to presenting PRO-CTCAE data. In modeling, the ToxT approach may be a good compromise compared with more sophisticated analyses.
Novel Ionizable Lipid Nanoparticles for SARS‐CoV‐2 Omicron mRNA Delivery
Authors: Jinrong Long, Changxiao Yu, Honglei Zhang, Yiming Cao, Ye Sang, Haitao Lu, Zhen Zhang, Xin Wang, Huanyu Wang, Gengshen Song, Jing Yang, Shengqi Wang
Journal: Advanced Healthcare Materials (2023)

mRNA-based therapy has emerged as the most promising nucleic acid therapy in the fight against COVID-19. However, a safe and efficacious systemic delivery remains a challenge for mRNA therapy. Lipid nanoparticles (LNPs) are currently widely used in mRNA delivery vehicles. Here, a series of ionizable LNPs is rationally designed. YK009-LNP is an optimal delivery platform to carry mRNA. YK009-LNP exhibits higher mRNA delivery efficiency, a more favorable biodistribution pattern, and better safety than the approved MC3-LNP. In addition, mRNA encoding severe acute respiratory syndrome coronavirus 2 Omicron receptor binding domain protein is synthesized and intramuscular administration of mice with YK009-LNP-Omicron mRNA induces a robust immune response and immune protective effect. A novel mRNA delivery vehicle with more powerful delivery efficiency and better safety than the approved LNPs is provided here.
Nanoscale Hafnium Metal–Organic Frameworks Enhance Radiotherapeutic Effects by Upregulation of Type I Interferon and TLR7 Expression
Authors: Eunseo Choi, Madeleine Landry, Nathan Pennock, Megan Neufeld, Katherine Weinfurter, Andrea Goforth, Joshua Walker, Conroy Sun
Journal: Advanced Healthcare Materials (2023)

Abstract Recent preclinical and clinical studies have highlighted the improved outcomes of combination radiotherapy and immunotherapy. Concurrently, the development of high‐Z metallic nanoparticles as radiation dose enhancers has been explored to widen the therapeutic window of radiotherapy and potentially enhance immune activation. In this study, folate‐modified hafnium‐based metal–organic frameworks (HfMOF‐PEG‐FA) are evaluated in combination with imiquimod, a TLR7 agonist, as a well‐defined interferon regulatory factor (IRF) stimulator for local antitumor immunotherapy. The enhancement of radiation dose deposition by HfMOF‐PEG‐FA and subsequent generation of reactive oxygen species (ROS) deregulates cell proliferation and increases apoptosis. HfMOF‐PEG‐FA loaded with imiquimod (HfMOF‐PEG‐FA@IMQ) increases DNA double‐strand breaks and cell death, including apoptosis, necrosis, and calreticulin exposure, in response to X‐ray irradiation. Treatment with this multipronged therapy promotes IRF stimulation for subsequent interferon production within tumor cells themselves. The novel observation is reported that HfMOF itself increases TLR7 expression, unexpectedly pairing immune agonist and receptor upregulation in a tumor intrinsic manner, and supporting the synergistic effect observed with the γ H2AX assay. T‐cell analysis of CT26 tumors following intratumoral administration of HfMOF‐PEG‐FA@IMQ with radiotherapy reveals a promising antitumor response, characterized by an increase in CD8 + and proliferative T cells.
Host Recovery from Respiratory Viral Infection
Authors: Xiaoqin Wei, Harish Narasimhan, Bibo Zhu, Jie Sun
Journal: Annual Review of Immunology (2023)

Emerging and re-emerging respiratory viral infections pose a tremendous threat to human society, as exemplified by the ongoing COVID-19 pandemic. Upon viral invasion of the respiratory tract, the host initiates coordinated innate and adaptive immune responses to defend against the virus and to promote repair of the damaged tissue. However, dysregulated host immunity can also cause acute morbidity, hamper lung regeneration, and/or lead to chronic tissue sequelae. Here, we review our current knowledge of the immune mechanisms regulating antiviral protection, host pathogenesis, inflammation resolution, and lung regeneration following respiratory viral infections, mainly using influenza virus and SARS-CoV-2 infections as examples. We hope that this review sheds light on future research directions to elucidate the cellular and molecular cross talk regulating host recovery and to pave the way to the development of pro-repair therapeutics to augment lung regeneration following viral injury.
The Garrett Lee Smith Memorial Act: A Description and Review of the Suicide Prevention Initiative
Authors: David B. Goldston, Christine Walrath
Journal: Annual Review of Clinical Psychology (2023)

The Garrett Lee Smith (GLS) Memorial Act, continuously funded since 2004, has supported comprehensive, community-based youth suicide prevention efforts throughout the United States. Compared to matched communities, communities implementing GLS suicide prevention activities have lower population rates of suicide attempts and lower mortality among young people. Positive outcomes have been more pronounced with continuous years of implementation and in less densely populated communities. Cost analyses indicate that implementation of GLS suicide prevention activities more than pays for itself in reduced health care costs associated with fewer emergency department visits and hospitalizations. Although findings are encouraging, the heterogeneity of community suicide prevention programs and the lack of randomized trials preclude definitive determination of causal effects associated with GLS. The GLS initiative has never been brought fully to scale (e.g., simultaneously impacting all communities in the United States), so beneficial effects on nationwide suicide rates have not been realized.
18F-FDG PET/CT of a Rare Sternal Osteoblastoma in a Man With History of Lymphoma
Authors: Jie Liang, Wen-Shan Huang, Wen-Zhen Lan, Yong Li, Jie-Hua Xu
Journal: Clinical Nuclear Medicine (2023)

A 27-year-old man, with a history of non-Hodgkin lymphoma 8 years ago, was admitted due to 9 months of persistent sternal pain. Chest CT revealed a mass in the sternum. 18 F-FDG PET/CT was performed, demonstrating a radioactive accumulation mass in the sternum, accompanied by massive osteogenesis and osteolysis. Histological and immunohistochemical analysis of ultrasound-guided fine-needle aspiration biopsy samples confirmed the diagnosis of aggressive osteoblastoma. We present a rare case of aggressive sternal osteoblastoma, instead of lymphoma recurrence, on 18 F-FDG PET/CT in an adult with history of lymphoma.
Chimeric Antigen Receptor T-Cell Therapy of Neurolymphomatosis Monitored by FDG PET/CT
Authors: Siqi Li, Hongrong Wang, Guanyun Wang, Xia Lu, Jigang Yang
Journal: Clinical Nuclear Medicine (2023)

18 F-FDG PET/CT was performed to evaluate possible recurrent B-cell lymphoblastic lymphoma in a 34-year-old man. The images showed multiple foci of increased activity in the nerve root and peripheral nerve. A biopsy confirmed the diagnosis of neurolymphomatosis. After receiving chemotherapy, PET/CT showed progressive disease. The patient subsequently received the CD-19 chimeric antigen receptor T-cell therapy. A follow-up PET/CT acquired 30 days after chimeric antigen receptor T-cell therapy revealed no abnormal FDG activity.
Peritoneal Metastases From Prostate Carcinoma Treated With 177Lu-PSMA-I&amp;T
Authors: Larissa W. van Golen, Tom T.P. Seijkens, Jeantine M. de Feijter, Wouter Vogel
Journal: Clinical Nuclear Medicine (2023)

A 71-year-old man was referred for 177 Lu-PSMA therapy. He had metastatic castration-resistant prostate cancer, progressive on several treatment lines, with current PSA 260 μg/L and deteriorating condition. CT showed ascites with omental and peritoneal metastases, all positive on PSMA PET/CT. He was treated with 4 cycles of 7.4 GBq (0.2 Ci) 177 Lu-PSMA-I&T. Posttherapy scans showed good targeting of all metastases. After 4 cycles, PSA had dropped to 44 μ/L. Four months after the fourth cycle, the patients' general condition had significantly improved, and PSA had decreased to 7.0 μg/L.
Complementary Role of 18F-Fluciclovine PET/CT and 18F-NaF PET/CT in Detecting Prostate Cancer Metastasis
Authors: Feng Xu, Frank Liu, Wen Chen
Journal: Clinical Nuclear Medicine (2023)

We present different findings on 18 F-fluciclovine (Axumin) PET/CT and 18 F-NaF PET/CT images in a patient with prostate cancer metastasis. 18 F-Fluciclovine PET/CT scan showed intense uptake in left adrenal gland metastasis, only faint to mild uptake in multiple sclerotic osseous metastasis where 18 F-NaF bone PET/CT demonstrated intense uptake at these sites. Both examinations are needed to accurately evaluate visceral and osseous metastasis from prostate cancer.
FDG PET/CT in a Case of Primary Angiosarcoma of the Kidney
Authors: Jian Yang, Aisheng Dong, Shensheng Nian, Yonghan Peng, Changjing Zuo
Journal: Clinical Nuclear Medicine (2023)

Primary angiosarcoma of the kidney is a rare aggressive malignancy. We describe MRI and FDG PET/CT findings in a case of primary renal angiosarcoma with hepatic, pulmonary, and bony metastases. The large primary tumor showed extensive necrosis and increased FDG uptake in the nonnecrotic components. Multiple metastatic lesions in the liver, lung, and bones were detected by FDG PET/CT. Most of the hepatic metastases seen on MRI were missed on FDG PET/CT due to low FDG avidity.
A Persistent Left-Sided Superior Vena Cava Detected on a O-15-H2O PET/CT of the Heart
Authors: David Lyse Overgaard, Lars Poulsen Tolbod, Lars Christian Gormsen, Michael Alle Madsen
Journal: Clinical Nuclear Medicine (2023)

A persistent left-sided superior vena cava (PLSVC) is an uncommon finding with a prevalence of up to 0.5% in the general population. The PLSVC appears when the left anterior cardinal vein fails to regress as the ligament of Marshall during embryologic development. It is usually asymptomatic and discovered incidentally; however, its recognition is important because it might complicate invasive cardiovascular procedures. In this case, we report an incidental finding of a PLSVC detected on the O-15-H 2 O PET/CT of a patient who was referred for myocardial perfusion imaging.
68Ga-FAPI PET/MRI and 18F-FDG PET/CT in a Case With Extensive Portal Vein Tumor Thrombus
Authors: Xilan Yao, Weiting Liu, Xiaohong Ou
Journal: Clinical Nuclear Medicine (2023)

18 F-FDG PET/CT has been reported to be useful in differentiating tumor thrombus and bland thrombus. There are few reports on 68 Ga-FAPI PET imaging features of tumor thrombus. Herein, we report a 46-year-old man with extensive tumor thrombus in the portal vein due to hepatic malignancy on 18 F-FDG PET/CT and 68 Ga-FAPI PET/MRI.
Electrocatalytic Palladium Nanoclusters as Versatile Indicators of Bioassays: Rapid Electroanalytical Detection of SARS‐CoV‐2 by Reverse Transcription Loop‐Mediated Isothermal Amplification
Authors: Alejandro Rodríguez‐Penedo, Pablo Rioboó‐Legaspi, Andrea González‐López, Ana Lores‐Padín, Rosario Pereiro, María del Mar García‐Suárez, María Dolores Cima‐Cabal, Estefanía Costa‐Rama, Beatriz Fernández, M. Teresa Fernández‐Abedul
Journal: Advanced Healthcare Materials (2023)

Quantitative polymerase chain reaction (qPCR) is considered the gold standard for pathogen detection. However, improvement is still required, especially regarding the possibilities of decentralization. Apart from other reasons, infectious diseases demand on-site analysis to avoid pathogen spreading and increase treatment efficacy. In this paper, the detection of SARS-CoV-2 is carried out by reverse transcription loop-mediated isothermal amplification, which has the advantage of requiring simple equipment, easily adaptable to decentralized analysis. It is proposed, for the first time, the use of palladium nanoclusters (PdNCs) as indicators of the amplification reaction at end point. The pH of the medium decreases during the reaction and, in turn, a variation in the catalytic activity of PdNCs on the oxygen reduction reaction (ORR) can be electrochemically observed. For the detection, flexible and small-size screen-printed electrodes can be premodified with PdNCs, which together with the use of a simple and small electrochemical equipment would greatly facilitates their integration in field-deployable devices. This would allow a faster detection of SARS-CoV-2 as well as of other future microbial threats after an easy adaptation.
Effects of Androgen Deprivation Therapy on Prostate Cancer Outcomes According to Competing Event Risk: Secondary Analysis of a Phase 3 Randomised Trial
Authors: Loren K. Mell, Stephanie L. Pugh, Christopher U. Jones, Tyler J. Nelson, Kaveh Zakeri, Brent S. Rose, Kenneth L. Zeitzer, Elizabeth M. Gore, Jean-Paul Bahary, Luis Souhami, Jeff M. Michalski, Alan C. Hartford, Mark V. Mishra, Mack Roach, Matthew B. Parliament, Kwang N. Choi, Thomas M. Pisansky, Siraj M. Husain, Shawn C. Malone, Eric M. Horwitz, Felix Feng
Journal: European Urology (2023)
Artificial cilia for soft and stable surface covalent immobilization of bone morphogenetic protein-2
Authors: Qi Gan, Lina Chen, Ho-Pan Bei, Sze-Wing Ng, Han Guo, Guoqiang Liu, Hao Pan, Changsheng Liu, Xin Zhao, Zijian Zheng
Journal: Bioactive Materials (2023)

Preservation of growth factor sensitivity and bioactivity (e.g., bone morphogenetic protein-2 (BMP-2)) post-immobilization to tissue engineering scaffolds remains a great challenge. Here, we develop a stable and soft surface modification strategy to address this issue. BMP-2 (a model growth factor) is covalently immobilized onto homogeneous poly (glycidyl methacrylate) (PGMA) polymer brushes which are grafted onto substrate surfaces (Au, quartz glass, silica wafer, or common biomaterials) via surface-initiated atom transfer radical polymerization. This surface modification method multiplies the functionalized interfacial area; it is simple, fast, gentle, and has little effect on the loaded protein owing to the cilia motility. The immobilized BMP-2 (i-BMP-2) on the surface of homogeneous PGMA polymer brushes exhibits excellent bioactivity (⁓87% bioactivity of free BMP-2 in vitro and 20%-50% higher than scaffolds with free BMP-2 in vivo), with conformation and secondary structure well-preserved after covalent immobilization and ethanol sterilization. Moreover, the osteogenic activity of i-BMP-2 on the nanoline pattern (PGMA-poly (N-isopropylacrylamide)) shows ⁓110% bioactivity of free BMP-2. This is superior compared to conventional protein covalent immobilization strategies in terms of both bioactivity preservation and therapeutic efficacy. PGMA polymer brushes can be used to modify surfaces of different tissue-engineered scaffolds, which facilitates in situ immobilization of growth factors, and accelerates repair of a wide range of tissue types.
Open‐label, Phase 2 study of roxadustat for the treatment of anemia in patients receiving chemotherapy for non‐myeloid malignancies
Authors: John Glaspy, Nashat Y. Gabrail, Patricia Locantore‐Ford, Tyson Lee, Katharina Modelska, Vivek Samal, David H. Henry
Journal: American Journal of Hematology (2023)

Anemia is a common side effect of myelosuppressive chemotherapy; however, chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in this setting. This open-label Phase 2 study included patients with non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had planned concurrent myelosuppressive chemotherapy for ≥8 additional weeks. Oral roxadustat was administered for ≤16 weeks (starting dose 2.0 or 2.5 mg/kg, then titrated every 4 weeks). The primary efficacy endpoint was mean maximum change in Hb within 16 weeks of baseline without red blood cell (RBC) transfusion. Patients were assigned to roxadustat 2.0 (n = 31) or 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The mean (standard deviation) maximum Hb change from baseline without RBC transfusion was 2.4 (1.5) and 2.5 (1.5) g/dL in the roxadustat 2.0 and 2.5 mg/kg groups, respectively. Median (range) time to Hb increase of ≥2 g/dL was 71 (57-92) days. Twelve patients (14.5%) had RBC transfusions (Week 5 to the end of treatment). Roxadustat was efficacious regardless of tumor type and chemotherapy regimen. Deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 14 (15.2%) and nine (9.8%) patients, respectively, and three had serious adverse events attributed to roxadustat in the opinion of the investigators (PE: n = 2 [2.2%]; DVT: n = 1 [1.1%]). Roxadustat increased Hb in patients with CIA regardless of tumor type and chemotherapy regimen. Adverse events were consistent with observations in patients with advanced-stage malignancies.
Bone microenvironment regulative hydrogels with ROS scavenging and prolonged oxygen-generating for enhancing bone repair
Authors: Han Sun, Juan Xu, Yangyufan Wang, Siyu Shen, Xingquan Xu, Lei Zhang, Qing Jiang
Journal: Bioactive Materials (2023)

Large bone defects resulting from fractures and disease are a major clinical challenge, being often unable to heal spontaneously by the body's repair mechanisms. Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration. However, replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells. Therefore, reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair. Herein, we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels (CPP-L/GelMA) as a "bone microenvironment regulative hydrogel" to reverse the hypoxic microenvironment in bone defects region. CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase (CAT) and ROS-responsive oxygen-releasing nanoparticles (PFC@PLGA/PPS) co-loaded liposome (CCP-L) and GelMA hydrogels. Under hypoxic condition, CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks. The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis. Finally, CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway. Hence, CPP-L/GelMA, as a bone microenvironment regulative hydrogel for bone tissue respiration, can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region, possessing of great clinical therapeutic potential.
The genetic contribution of inflammation to the increased risk of cardiovascular disease in rheumatoid arthritis: comment on the article by Yuan et al
Authors: Raquel López‐Mejías, Miguel Ángel González‐Gay
Journal: Arthritis & Rheumatology (2023)

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Heightened Proinflammatory Glycosylation of <i>Borrelia burgdorferi</i> IgG Antibodies in Synovial Fluid in Patients With Antibiotic‐Refractory Lyme Arthritis
Authors: Jurgen T. Sanes, Catherine E. Costello, Allen C. Steere
Journal: Arthritis & Rheumatology (2023)

Objective Terminal glycans on the Fc portion of IgG antibodies are critical for antibody‐triggered, proinflammatory or antiinflammatory responses. We undertook this study to compare glycan profiles of total IgG1 and Borrelia burgdorferi (Bb)–specific IgG1 antibodies in patients with oral antibiotic–responsive or antibiotic‐refractory Lyme arthritis (LA). Methods Following affinity‐column processing, glycan profiles of IgG antibodies were determined in serum and synovial fluid (SF) samples of 21 LA patients using glycoblotting with hydrazide glycan enrichment and determination of glycan structure by matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry. Correlations between glycan profiles and treatment outcomes were analyzed. Results Compared with patients with antibiotic‐refractory LA, those with antibiotic‐responsive LA had total and Bb‐specific IgG1 antibody glycans with less intense inflammatory profiles, containing lower percentages of N ‐acetylglucosamine (GlcNAc) and bisecting GlcNAc and higher percentages of galactose and fucose. In contrast, patients with antibiotic‐refractory LA prior to receiving IV antibiotic therapy had total IgG1 and Bb IgG1 antibodies with maximal, minimally opposed, proinflammatory glycan profiles, containing high percentages of GlcNAc and bisecting GlcNAc, intermediate percentages with galactose and fucose, and low percentages with N ‐acetylneuraminic acid (sialic acid). Patients with refractory LA who were first seen with synovitis after receiving IV antibiotic therapy still had Bb IgG1 antibodies with strongly inflammatory glycan profiles, but their inflammatory potential appeared to be waning. Conclusion Patients with oral antibiotic–responsive LA had Bb IgG1 antibodies with more balanced proinflammatory/antiinflammatory glycan profiles, whereas patients with antibiotic‐refractory LA had Bb IgG1 antibodies with maximal, minimally opposed, proinflammatory glycan profiles. Among patients with antibiotic‐refractory LA, antibodies with this unbalanced inflammatory glycan profile may have a role in sustaining maladaptive joint inflammation.